(i) Field of the Invention
The present invention relates to a process for preparing hypocholesteremic products, e.g., Lovastatin and Mevastatin.
(ii). Description of the Prior Art
High blood cholesterol levels are recognized as being one of the main causes of cardiopathy, e.g., cardiac infarction, arteriosclerosis or hyperlipaemia.
It is currently believed that a causative factor in such diseases is the deposition of cholesterol in the body, particularly within the arteries. As a result, considerable research has been undertaken with a view to discovering physiologically acceptable substances which are capable of inhibiting cholesterol biosynthesis and thus are capable of reducing blood cholesterol levels. Several patents have issued directed to such compounds and their process for production.
In one such patent, namely U.S. Pat. No. 3,983,140 patented Sep. 28, 1976 by A. Endo et al and its corresponding Canadian Patent 1,046,439 patented Jan. 16, 1979, a physiologically-active substances of the Formula ##STR1## wherein R is hydrogen atom, hydroxy group or 2-methylbutyryloxy group, had been found to have cholesterol- and lipid-lowering effects in blood and liver and thus had utility as hypocholesteremic and hypolipemic medicaments. Such compounds were obtained by cultivation of a species of microorganisms belonging to the genus Penicillium, i.e., Penicillium citrinum in a culture medium and subsequent recovery thereof from a cultured broth.
In another such patent, namely U.S. Pat. No. 4,231,938, patented Nov. 4, 1980 by R. L. Monaghan et al, a compound having the lactone structure ##STR2## as well as its free hydroxy acid form had been found to form a class of highly active hypocholesteremic and hypolipemic medicaments. Such compounds were isolated after cultivation of a microorganism belonging to the genus Aspergillus in a culture medium.
In still another such patent, namely Canadian Patent 1,129,794 patented Aug. 17, 1982 by A. Endo, a compound having the formula ##STR3## was found to be an antihypercholesteraemic agent. Such compound was prepared by cultivating a microorganism of the genus Monascus, e.g., Monascus ruber, particularly Monascus ruber strain 1005 (FERM 4822) in a suitable culture medium.
In yet another such patent, namely Canadian Patent 1,161,380 patented Jan. 31, 1984 by R. L. Monaghan et al, hypocholesteremic products were obtained from the cultivation of a microfungus of the species Aspergillus, e.g., Aspergillus terreus.
One commercially-available such compound is Lovastatin, having the formula ##STR4## This compound has been found to be a potent inhibitor of HMB-CoA reductase, the rate controlling enzyme in cholesterol biosynthesis. Fermentation procedures for the preparation of this compound have been patented, namely in the above-identified Canadian Patent No. 1,046,439.
Another commercially-available such compound is Mevastatin having the formula ##STR5## this compound also has been found to be a potent inhibitor of HMG-CoA reductase, the rate controlling enzyme in cholesterol biosynthesis. One patented procedure for the preparation of such compound is the above-identified U.S. Pat. No. 3,983,140.